The HCV epidemic is not a new one, yet it has been ignored for some time, while HIV has been the epidemic dealt with on a global and national levels. This silent epidemic, which kills more people than AIDS, is now rising to the public awareness. This is due to several factors such as the HIV-HCV co infection, HCV spreading among HIV positive people and other at risk populations, and the recent emergence of new drugs for treating HCV. These drugs, and hopefully others in the pipeline, have lower toxicity and a shorter duration of treatment—thus making the argument for early treatment stronger, offering a potential for not only curtailing the epidemic, but also to eradicate it. We have gained much insight into the combat of blood born disease while working with HIV, and the lessons learnt there should be applied to HCV, such as the Test & Treat program and the efforts to identify all carriers of the infection.
However, the HCV epidemic presents us with new and different challenges regarding diagnosis, and this in its turn affects treatment decisions:
1. A long seronegative window period—unlike most infections, antibodies against HCV do not appear within 7-10 days of the infection. There is a seronegative window period of several months and thus a negative antibody test does not provide a confirmed, negative, diagnosis. Since the virus resides mainly in the liver, its absence from the blood, at detectable levels also does not constitute a clean bill of health. In individuals with some general immune suppression (e.g. pregnant women, MSM, hemodialysis patients), the window period is even longer. The current antibody tests for HCV antibodies detect only IgG which delays the diagnosis even further. A tool which enables early detection of HCV infection is critical in high risk groups, as seronegative results require repeat testing several weeks or months later, and the return rate for repeat testing is very low. Solving the problem of the long seronegative window period is important for tracking/mapping a potential HCV outbreak. Without early detection tools, the most recent infections are missed, thus giving “delayed” view of the current outbreak and its current scope. This seronegative window period is an immunological enigma as HCV antigens are very immunogenic, and antibodies should have been detectable within days of infection.
2. High (and variable) levels of false positive results—the current HCV diagnostic assays have a relatively high levels of false positives' rate. To add to the complexity of deriving true HCV prevalence information from testing programs and surveys, the false positive rate varies from population to population, and from country to country. This is a major concern as it means, on the epidemiological level that we would be over-estimating prevalence (and in a varying, and unknown, degree) in different population around the world. On another level, the low specificity of the antibody assays affects the blood supply, as it causes a loss of good/safe blood, and the temporary deferral of the donor leads to additional potential loss of blood donations.
The high level of ‘noise’ in the HCV antibody assays is also a complicating factor in the efforts to develop a diagnostic kit which will detect anti HCV IgM antibodies, efforts which have not been successful to date.
3. The routine antibody testing in serum/plasma does not differentiate between current/chronic infection and cleared/resolved infection. This is important in HCV infection as 15-25% of new HCV infections are spontaneously resolved. Those who resolved the infection still test positive on the antibody assays for many years following the clearance of the virus, as there are very high levels of HCV antibodies in the blood, and IgG has a half-life 21 days. Using molecular assays for the detection of viral genome, offers only a partial solution as the lack of detection of HCV viral genome in measurable levels in the blood is not a clear indication for the state of the infection in the liver. Thus, current assays do not provide a clear diagnosis of current HCV infection.